Phylogenetic analysis of multiprobe fluorescence in situ hybridization data from tumor cell populations.

Phylogenetic analysis of multiprobe fluorescence in situ hybridization data from tumor cell populations.
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DOI:
10.1093/bioinformatics/btt205
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发表时间:
2013-07-01
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
Schwartz R
Schwartz R
中科院分区:
其他
文献类型:
--
作者:
Chowdhury SA;Shackney SE;Heselmeyer-Haddad K;Ried T;Schäffer AA;Schwartz R

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动机:实体瘤的发展和进展可归因于突变过程,其通常包括基因或基因组区域拷贝数的变化。虽然单个肿瘤内细胞的比较显示出广泛的异质性,但通过比较肿瘤的多个区域或细胞,可以识别其进化过程的重复特征。用于研究个体肿瘤可能进展的有用数据来源是荧光原位杂交(FISH),其允许对数百个单细胞中的几个基因的拷贝数进行计数。然而,需要新的算法来解释这些数据,以从单细胞的状态重建可能的进化轨迹,并促进肿瘤进化的分析。结果如下:在这篇文章中,我们开发系统发育的方法来推断可能的模型,使用FISH拷贝数数据的肿瘤进展,并将其应用到两种癌症类型的FISH数据的研究。基于树的模型的拓扑特征的统计分析提供了与先前文献一致的可能的肿瘤进展途径的见解。此外,从所得到的聚类分析中得到的树统计数据可以用作预测方法的特征。相对于非结构化基因拷贝数数据,这导致预测肿瘤状态和未来转移的准确性提高。供货情况:建立FISH树的软件源代码(FISH trees)以及这里检查的宫颈癌和乳腺癌数据可在www.example.com上获得ftp://ftp.ncbi.nlm.nih.gov/pub/FISHtrees。联系方式:sachowdh@andrew.cmu.edu补充信息:补充数据可从生物信息学在线网站获得。
Motivation: Development and progression of solid tumors can be attributed to a process of mutations, which typically includes changes in the number of copies of genes or genomic regions. Although comparisons of cells within single tumors show extensive heterogeneity, recurring features of their evolutionary process may be discerned by comparing multiple regions or cells of a tumor. A useful source of data for studying likely progression of individual tumors is fluorescence in situ hybridization (FISH), which allows one to count copy numbers of several genes in hundreds of single cells. Novel algorithms for interpreting such data phylogenetically are needed, however, to reconstruct likely evolutionary trajectories from states of single cells and facilitate analysis of tumor evolution. Results: In this article, we develop phylogenetic methods to infer likely models of tumor progression using FISH copy number data and apply them to a study of FISH data from two cancer types. Statistical analyses of topological characteristics of the tree-based model provide insights into likely tumor progression pathways consistent with the prior literature. Furthermore, tree statistics from the resulting phylogenies can be used as features for prediction methods. This results in improved accuracy, relative to unstructured gene copy number data, at predicting tumor state and future metastasis. Availability: Source code for software that does FISH tree building (FISHtrees) and the data on cervical and breast cancer examined here are available at ftp://ftp.ncbi.nlm.nih.gov/pub/FISHtrees. Contact: sachowdh@andrew.cmu.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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